Telomere shortening is an in vivo marker of myocyte replication and aging

To determine whether adult cardiac myocytes are capable of multiple divisio ns and whether this form of growth is restricted to a subpopulation of cell s that retain this capacity with age, telomere lengths were measured in myo cyte nuclei isolated from the left ventricle of fetal and neonatal Fischer 344 rats and rats at 4, 12, and 27 months after birth. Two independent meth odologies were used for this analysis: laser scanning cytometer and confoca l microscopy. In each case, fluorescence intensity of a peptide nucleic aci d probe specific for telomeric sequence was evaluated. The two techniques y ielded comparable results. Telomeric shortening increased with age in a sub group of myocytes that constituted 16% of the entire cell population. In th e remaining nondividing cells, progressive accumulation of a senescent asso ciated nuclear protein, p16(INK4), was evidenced. In conclusion, a signific ant fraction of myocytes divides repeatedly from birth to senescence, count eracting the continuous death of cells in the aging mammalian rat heart.